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Journal of Pharmacology And Experimental Therapeutics, Vol. 145, Issue 1, 102-112, 1964
Copyright © 1964 by American Society for Pharmacology and Experimental Therapeutics

STUDIES ON THE ABSORPTION, METABOLISM AND EXCRETION OF METHYLDOPA AND OTHER CATECHOLS AND THEIR INFLUENCE ON AMINO ACID TRANSPORT IN RATS

J. A. Young 1 and K. D. G. Edwards 1

1 Medical Research Department, Kanematsu Memorial Institute, Sydney Hospital, Sydney, N.S.W., Australia

The absorption, excretion, metabolism and effects on amino acid transport of l-methyldopa, d-methyldopa, dl-dopa, l-methyldopamine and dopamine have been studied in rats by means of paper chromatography of bile, plasma and urine. The results suggested that the synthetic methyldopa was poorly transported by the alimentary and renal transport mechanisms normally available to amino acids. However l-methyldopa was found to be more readily absorbed from the gut than the d-isomer.

Methyldopa, dopa, and their corresponding amines were found to produce specific reversible amino acidurias involving histidine, taurine, serine, alanine, and glutamic acid most consistently. This was postulated to be the result of competition in the nephron for transport between the catechols and those amino acids believed to share the neutral transport system.

After methyldopa therapy the main excretory product in the urine was the drug itself but small quantities of the 3-O-methyl derivative and very small amounts of methyldopamine and its 3-O-methyl derivative were also detected. Glucuronides of methoxymethyldopa and methoxymethyldopamine were also found in small amounts. When animals were given methyldopamine, dopa or dopamine the most prominent excretory products were glucuronides. d-Methyldopa was 3-O-methylated to give methoxymethyldopa but not decarboxylated to the amine. This was thought to be the reason for its therapeutic inactivity.

Methyldopa and one metabolite thought to be a glucuronide derivative were excreted in the bile in small amounts relative to urinary concentrations of these substances. Effects on biliary amino acid patterns were slight.

Accepted on February 21, 1964




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